Effects of tenofovir disoproxil fumarate in hepatitis B e antigen-positive patients with normal levels of alanine aminotransferase and high levels of hepatitis B virus DNA

Henry L.Y. Chan, Chi Kuen Chan, Aric Josun Hui, Sing Chan, Fred Poordad, Ting Tsung Chang, Philippe Mathurin, John F. Flaherty, Lanjia Lin, Amy Corsa, Anuj Gaggar, G. Mani Subramanian, John G. McHutchison, Sam Lee, Edward J. Gane

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83 Scopus citations

Abstract

Background & Aims Little is known about the benefit of antiviral therapy for hepatitis B e antigen (HBeAg)-positive patients with high viral load and normal levels of alanine aminotransferase. We evaluated the effects of single and combination therapies in immune-tolerant patients with chronic hepatitis B. Methods In a double-blind study, nucleos(t)ide-naïve patients with high levels of hepatitis B virus (HBV) DNA who were positive for HBeAg and had normal levels of alanine aminotransferase were randomly assigned to groups given either oral tenofovir disoproxil fumarate (TDF, 300 mg) and placebo (n = 64) or a combination of TDF (300 mg) and emtricitabine (200 mg, n = 62) for 192 weeks. The primary end point was proportion of patients with serum levels of HBV DNA <69 IU/mL at week 192. Results The study population (mean age was 33 years; 89% were Asian) was predominantly infected with HBV genotypes B and C (93%), 99% were HBeAg positive with a mean baseline level of HBV DNA of 8.41 log10 IU/mL. At week 192, 55% of patients (35 of 64) in the TDF+placebo group and 76% of patients (47 of 62) in the TDF+emtricitabine group had levels of HBV DNA <69 IU/mL (P =.016). No patients were found to have viral resistance to therapy. HBeAg seroconversion occurred in 3 patients (5%), all in the TDF+placebo group; no patient had loss of hepatitis B surface antigen. In multivariate analysis, female sex (odds ratio = 7.05; P =.002) and TDF+emtricitabine treatment (odds ratio = 3.9; P =.01) were associated with a favorable response. Both regimens were well tolerated. Conclusions In HBeAg-positive patients with chronic HBV infection, high viral loads, normal levels of alanine aminotransferase, and therapy with the combination of TDF and emtricitabine provided better viral suppression than TDF alone, although rates of HBeAg seroconversion and hepatitis B surface antigen loss were low.

Original languageEnglish (US)
Pages (from-to)1240-1248
Number of pages9
JournalGastroenterology
Volume146
Issue number5
DOIs
StatePublished - May 2014
Externally publishedYes

Keywords

  • Combination Therapy
  • FTC
  • HBsAg
  • Immune Tolerant
  • Keywords

ASJC Scopus subject areas

  • Hepatology
  • Gastroenterology

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    Chan, H. L. Y., Chan, C. K., Hui, A. J., Chan, S., Poordad, F., Chang, T. T., Mathurin, P., Flaherty, J. F., Lin, L., Corsa, A., Gaggar, A., Subramanian, G. M., McHutchison, J. G., Lee, S., & Gane, E. J. (2014). Effects of tenofovir disoproxil fumarate in hepatitis B e antigen-positive patients with normal levels of alanine aminotransferase and high levels of hepatitis B virus DNA. Gastroenterology, 146(5), 1240-1248. https://doi.org/10.1053/j.gastro.2014.01.044